2,2-Difluoroethanamine → [3-(Tert-butyl-dimethyl-silanyloxymethyl)-4-chloro-benzyl]-(2,2-difluoro-ethyl)-amine

HRID 1715395노트

반응식

HRID 1715395 반응식
[F:1][CH:2]([F:5])[CH2:3][NH2:4].[C:6]([SiH2:10][O:11][C:12]([CH3:23])([CH3:22])[C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[Cl:21])[CH:16]=O)([CH3:9])([CH3:8])[CH3:7].[BH4-].[Na+]>CO>[C:6]([SiH2:10][O:11][C:12]([CH3:23])([CH3:22])[C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[Cl:21])[CH2:16][NH:4][CH2:3][CH:2]([F:5])[F:1])([CH3:9])([CH3:7])[CH3:8]

참가 물질

5

반응물 3

HCID 1362742,2-DifluoroethanamineHCID 4311764Sodium borohydrideHCID 1373299173-(tert-Butyl-dimethyl-silanyloxymethyl)-4-chloro-benzaldehyde

생성물 1

HCID 137329918[3-(Tert-butyl-dimethyl-silanyloxymethyl)-4-chloro-benzyl]-(2,2-difluoro-ethyl)-amine수율 100.9%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

2,2-Difluoroethylamine (660 mg, 7.90 mmol) was added to a sol. of 3-(tert-butyl-dimethyl-silanyloxymethyl)-4-chloro-benzaldehyde (1.50 g, 5.27 mmol) in MeOH (53 mL). The mixture was heated to reflux for 4 h, and was allowed to cool down to rt. NaBH4 (300 mg, 7.90 mmol) was added carefully by portions, and the mixture was stirred for 1 h. The solvents were removed under reduced pressure, and the resulting oil was diluted with EtOAc. The mixture was washed with aq. sat. NaHCO3 and brine. The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure to yield [3-(tert-butyl-dimethyl-silanyloxymethyl)-4-chloro-benzyl]-(2,2-difluoro-ethyl)-amine (1.86 g) as a clear crude oil that was used further directly. This crude material was dissolved in CH2Cl2 (53 mL), and DIPEA (2.7 mL, 15.6 mmol) was added, followed by Boc2O (1.70 g, 7.90 mmol). The mixture was stirred at rt for 1 h. The mixture was diluted with CH2Cl2 (50 mL), and washed with aq. 1M HCl, aq. sat. NaHCO3, and brine. The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (EtOAc/heptane 5:95) yielded the title compound (2.27 g, 96%). LC-MS: tR=1.22 min.

후처리

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 4 h
  3. customThe solvents were removed under reduced pressure
  4. additionthe resulting oil was diluted with EtOAc
  5. washThe mixture was washed with aq. sat. NaHCO3 and brine
  6. dry with materiallayer was dried over MgSO4
  7. filtrationfiltered
  8. customthe solvents were removed under reduced pressure

출처 및 근거

ORD 기록
ord-3eac23d4eadd4f9da685f5b72e937b64
출처 데이터셋
uspto-grants-2010_09
특허 번호
US07799805B2

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